ADH1A

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Jian Guan - One of the best experts on this subject based on the ideXlab platform.

  • Expression profile and co-expression analysis of ADH1A in human solid tumors.
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533 Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so it aroused our interest in studying these genes to find out their functions and biological process within different solid tumors. Methods: Paired tumor and normal tissues gathered from 38 tumor patients, and 5 male BALB/c mice tissues were collected and Immunohistochemistry (IHC) assay was performed. The expression of ADH1A at RNA level in normal tissues and pan-solid tumors and the main functions of ADH1A in different solid tumors were analyzed by Bioinformatics mining. Results: At the RNA level, ADH1A was highly expressed in normal hepatocytes and was expressed lower in the tumor tissues than in the adjacent normal tissues or the corresponding normal tissues, suggesting the At the protein level, ADH1A was expressed to varying degrees in human alveoli, kidney, stomach, colon, and rectum. We predicted three major conserved functions of ADH1A, including angiogenesis, cell adhesion, and leukocyte migration function which might influence the prognosis of the immunotherapy and the immune response, and constructed an upstream regulation network of ADH1A and a downstream protein network. Besides, we also explored the functional differences of ADH1A in lung adenocarcinoma and lung squamous cell carcinoma and its effect on overall survival. And for investigating ADH1A, the BALB/c mice might be an option to consider in constructing an animal model of gastric cancer (GC), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Conclusions: ADH1A has potential diagnostic and prognostic value in various solid tumors. Our findings highlight new avenues for further investigation of ADH1A biology process and provide a novel potential prognostic biomarker of immunotherapy.

  • expression profile and co expression analysis of ADH1A in human solid tumors
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so...

Wenqi Huang - One of the best experts on this subject based on the ideXlab platform.

  • Expression profile and co-expression analysis of ADH1A in human solid tumors.
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533 Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so it aroused our interest in studying these genes to find out their functions and biological process within different solid tumors. Methods: Paired tumor and normal tissues gathered from 38 tumor patients, and 5 male BALB/c mice tissues were collected and Immunohistochemistry (IHC) assay was performed. The expression of ADH1A at RNA level in normal tissues and pan-solid tumors and the main functions of ADH1A in different solid tumors were analyzed by Bioinformatics mining. Results: At the RNA level, ADH1A was highly expressed in normal hepatocytes and was expressed lower in the tumor tissues than in the adjacent normal tissues or the corresponding normal tissues, suggesting the At the protein level, ADH1A was expressed to varying degrees in human alveoli, kidney, stomach, colon, and rectum. We predicted three major conserved functions of ADH1A, including angiogenesis, cell adhesion, and leukocyte migration function which might influence the prognosis of the immunotherapy and the immune response, and constructed an upstream regulation network of ADH1A and a downstream protein network. Besides, we also explored the functional differences of ADH1A in lung adenocarcinoma and lung squamous cell carcinoma and its effect on overall survival. And for investigating ADH1A, the BALB/c mice might be an option to consider in constructing an animal model of gastric cancer (GC), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Conclusions: ADH1A has potential diagnostic and prognostic value in various solid tumors. Our findings highlight new avenues for further investigation of ADH1A biology process and provide a novel potential prognostic biomarker of immunotherapy.

  • expression profile and co expression analysis of ADH1A in human solid tumors
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so...

Joel Gelernter - One of the best experts on this subject based on the ideXlab platform.

  • Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases
    Human Genetics, 2012
    Co-Authors: Dawei Li, Hongyu Zhao, Joel Gelernter
    Abstract:

    The alcohol dehydrogenase 1C (ADH1C) subunit is an important member of the alcohol dehydrogenase family, a set of genes that plays a major role in the catabolism of ethanol. Numerous association studies have provided compelling evidence that ADH1C gene variation (formerly ADH3 ) is associated with altered genetic susceptibility to alcoholism and alcohol-related liver disease, cirrhosis, or pancreatitis. However, the results have been inconsistent, partially, because each study involved a limited number of subjects, and some were underpowered. Using cumulative data over the past two decades, this meta-analysis (6,796 cases and 6,938 controls) considered samples of Asian, European, African, and Native American origins to examine whether the aggregate genotype provide statistically significant evidence of association. The results showed strong evidence of association between ADH1C Ile350Val (rs698, formerly ADH1C *1/*2) and alcohol dependence (AD) and abuse in the combined studies. The overall allelic (Val vs. Ile or *2 vs. *1) P value was 1 × 10^−8 and odds ratio (OR) was 1.51 (1.31, 1.73). The Asian populations produced stronger evidence of association with an allelic P value of 4 × 10^−33 [OR 2.14 (1.89, 2.43)] with no evidence of heterogeneity, and the dominant and recessive models revealed even stronger effect sizes. The strong evidence remained when stricter criteria and sub-group analyses were applied, while Asians always showed stronger associations than other populations. Our findings support that ADH1C Ile may lower the risk of AD and alcohol abuse as well as alcohol-related cirrhosis in pooled populations, with the strongest and most consistent effects in Asians.

  • ADH1A variation predisposes to personality traits and substance dependence
    American Journal of Medical Genetics, 2010
    Co-Authors: Joel Gelernter, Henry R. Kranzler, Murray B Stein, Huiping Zhang, James Poling
    Abstract:

    Human personality traits are strong predictors or characteristics of many psychiatric disorders including substance dependence (SD). Recently, significant associations between alcohol dehydrogenase type 1A gene (ADH1A) and SD have been reported, which led us to investigate the impact of ADH1A variation on personality traits and risk of SD. Five hundred fifty-eight subjects with SD [398 European-Americans (EAs) and 160 African-Americans (AAs)], 517 college students (384 EAs and 133 European-origin Hispanics), and 448 healthy subjects (385 EAs, 48 AAs, and 15 European-origin Hispanics) participated. Personality traits were assessed in 247 subjects with SD (179 EAs and 68 AAs), all 517 college students, and 332 healthy subjects (285 EAs, 40 AAs, and 7 European-origin Hispanics). The relationships between ADH1A and personality traits were comprehensively examined using stepwise multivariate analysis of covariance (MANCOVA), and then decomposed by stepwise analysis of covariance (ANCOVA). The relationship between ADH1A and SD was examined using stepwise logistic regression analysis. Admixture effects on analyses were considered. Overall, Agreeableness and Conscientiousness were associated with the diplotypes, haplotypes, genotypes, and/or alleles of ADH1A in three of four phenotype groups including EA SD subjects, healthy subjects, and AA SD subjects (1.7 × 10−4 ≤ P ≤ 0.055), but not college students. Neuroticism was associated with diplotype, haplotypes and genotypes in AA SD subjects (0.001 ≤ P ≤ 0.031). In addition, SD was associated with diplotypes, haplotypes, genotypes, and/or alleles of ADH1A (0.008 ≤ P ≤ 0.060). The present study demonstrates that the ADH1A variation may contribute to the genetic component of variation in personality traits and SD. © 2009 Wiley-Liss, Inc.

  • ADH1A variation predisposes to personality traits and substance dependence.
    American journal of medical genetics. Part B Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2009
    Co-Authors: Joel Gelernter, Henry R. Kranzler, Murray B Stein, Huiping Zhang, James Poling
    Abstract:

    Human personality traits are strong predictors or characteristics of many psychiatric disorders including substance dependence (SD). Recently, significant associations between alcohol dehydrogenase type 1A gene (ADH1A) and SD have been reported, which led us to investigate the impact of ADH1A variation on personality traits and risk of SD. Five hundred fifty-eight subjects with SD [398 European-Americans (EAs) and 160 African-Americans (AAs)], 517 college students (384 EAs and 133 European-origin Hispanics), and 448 healthy subjects (385 EAs, 48 AAs, and 15 European-origin Hispanics) participated. Personality traits were assessed in 247 subjects with SD (179 EAs and 68 AAs), all 517 college students, and 332 healthy subjects (285 EAs, 40 AAs, and 7 European-origin Hispanics). The relationships between ADH1A and personality traits were comprehensively examined using stepwise multivariate analysis of covariance (MANCOVA), and then decomposed by stepwise analysis of covariance (ANCOVA). The relationship between ADH1A and SD was examined using stepwise logistic regression analysis. Admixture effects on analyses were considered. Overall, Agreeableness and Conscientiousness were associated with the diplotypes, haplotypes, genotypes, and/or alleles of ADH1A in three of four phenotype groups including EA SD subjects, healthy subjects, and AA SD subjects (1.7 x 10(-4)

  • Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans
    Human Molecular Genetics, 2006
    Co-Authors: Henry R. Kranzler, Shuang Wang, Nicholas J. Schork, Joel Gelernter
    Abstract:

    : Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with seven alcohol dehydrogenase (ADH) genes. The present study examines the relationship between these genes and DD. We genotyped 16 markers within the ADH gene cluster and 38 unlinked ancestry-informative markers in a case-control sample of 718 individuals. All markers were consistent with Hardy-Weinberg equilibrium in controls, but some markers showed Hardy-Weinberg disequilibrium in cases (minimal P = 0.002). Genotypes of many markers were associated with DD, both before and after controlling for admixture effects (minimal P < 1.0 x 10(-6)). Diplotype trend regression analysis showed that ADH5 and ADH6 genotypes, and diplotypes at ADH1A, ADH1B, ADH1C and ADH7 (minimal P = 0.002), were associated with DD in European-Americans and/or African-Americans. This first report of an allelic association of these loci with DD provides new insight into the mechanism of genetic risk for DD. These findings, obtained using a series of powerful and reliable analytic methods, may also help to explain the high rate of co-morbidity between AD and DD.

  • Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence.
    American Journal of Human Genetics, 2006
    Co-Authors: Henry R. Kranzler, Shuang Wang, Nicholas J. Schork, Joel Gelernter
    Abstract:

    The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and alcohol dependence (AD) have long been studied in many populations, but not comprehensively. In the present study, we genotyped 16 markers within the ADH gene cluster (including the ADH1A, ADH1B, ADH1C, ADH5, ADH6, and ADH7 genes), 4 markers within the ALDH2 gene, and 38 unlinked ancestry-informative markers in a case-control sample of 801 individuals. Associations between markers and disease were analyzed by a Hardy-Weinberg equilibrium (HWE) test, a conventional case-control comparison, a structured association analysis, and a novel diplotype trend regression (DTR) analysis. Finally, the disease alleles were fine mapped by a Hardy-Weinberg disequilibrium (HWD) measure (J). All markers were found to be in HWE in controls, but some markers showed HWD in cases. Genotypes of many markers were associated with AD. DTR analysis showed that ADH5 genotypes and diplotypes of ADH1A, ADH1B, ADH7, and ALDH2 were associated with AD in European Americans and/or African Americans. The risk-influencing alleles were fine mapped from among the markers studied and were found to coincide with some well-known functional variants. We demonstrated that DTR was more powerful than many other conventional association methods. We also found that several ADH genes and the ALDH2 gene were susceptibility loci for AD, and the associations were best explained by several independent risk genes.

Chen Wu - One of the best experts on this subject based on the ideXlab platform.

  • genetic variant repressing ADH1A expression confers susceptibility to esophageal squamous cell carcinoma
    Cancer Letters, 2017
    Co-Authors: Linna Peng, Jiang Chang, Xudong Huang, Yanjie Zhao, Jun Li, Mingming Shao, Chao Zhang, Cheng Li, Chen Wu
    Abstract:

    Abstracts Genome-wide association studies (GWAS) have discovered numerous genetic susceptibility loci including a cluster of alcohol dehydrogenase (ADH) gene family for esophageal squamous-cell carcinoma (ESCC). However, the underlying mechanism has not fully been elucidated. In this study, we integrated the GWAS data, gene-drinking interaction, expression quantitative trait locus (eQTL) analysis and biochemical experiments to clarify the specific mechanism of the polymorphisms in ADH loci. By imputation and eQTL analysis, we identified rs1154402C>G in intron 1 of ADH5 substantially associated with the expression levels of ADH1A. Association analysis showed that the rs1154402[G] allele was significantly associated with ESCC risk in drinkers (OR = 1.44, 95% CI = 1.20–1.73; P = 7.74 × 10−5) but not in nondrinkers (OR = 1.14, 95% CI = 0.93–1.37; P = .220). Furthermore, the ADH5 variant showed a significant interaction with drinking and the genetic variant near ALDH2 encoding the enzyme oxidizing acetaldehyde, a carcinogenic product resulted from alcohol oxidation catalyzed by ADHs. We demonstrated for the first time that rs1154402C>G change might create a silencer, repressing ADH1A transcription via long-range interaction with ADH1A promoter. These results suggest that genetic variant in ADH5 might confer alcohol drinkers susceptible to ESCC by down-regulation of ADH1A, which weakens alcohol catabolism.

Jihong Hwang - One of the best experts on this subject based on the ideXlab platform.

  • Expression profile and co-expression analysis of ADH1A in human solid tumors.
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533 Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so it aroused our interest in studying these genes to find out their functions and biological process within different solid tumors. Methods: Paired tumor and normal tissues gathered from 38 tumor patients, and 5 male BALB/c mice tissues were collected and Immunohistochemistry (IHC) assay was performed. The expression of ADH1A at RNA level in normal tissues and pan-solid tumors and the main functions of ADH1A in different solid tumors were analyzed by Bioinformatics mining. Results: At the RNA level, ADH1A was highly expressed in normal hepatocytes and was expressed lower in the tumor tissues than in the adjacent normal tissues or the corresponding normal tissues, suggesting the At the protein level, ADH1A was expressed to varying degrees in human alveoli, kidney, stomach, colon, and rectum. We predicted three major conserved functions of ADH1A, including angiogenesis, cell adhesion, and leukocyte migration function which might influence the prognosis of the immunotherapy and the immune response, and constructed an upstream regulation network of ADH1A and a downstream protein network. Besides, we also explored the functional differences of ADH1A in lung adenocarcinoma and lung squamous cell carcinoma and its effect on overall survival. And for investigating ADH1A, the BALB/c mice might be an option to consider in constructing an animal model of gastric cancer (GC), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Conclusions: ADH1A has potential diagnostic and prognostic value in various solid tumors. Our findings highlight new avenues for further investigation of ADH1A biology process and provide a novel potential prognostic biomarker of immunotherapy.

  • expression profile and co expression analysis of ADH1A in human solid tumors
    Journal of Clinical Oncology, 2020
    Co-Authors: Wenqi Huang, Mi Yang, Xixi Wu, Lu Yuan, Yuting Wu, Jihong Hwang, Jian Guan
    Abstract:

    e13533Background: The human alcohol dehydrogenase (ADH) gene family is associated with various solid cancers. It seems that the ADH1 gene cluster plays an important role in various solid tumors, so...